Case Presentation: A 58 year old previously healthy Nigerian female presented with a 6-week history of high-grade fevers, weakness, malaise, and a 10-pound weight loss. On physical exam she was found to have tachycardia, hypotension, fever (Temperature 103F), altered mental status and peripheral pitting edema. Her hospital course was complicated by hypotension and acute kidney injury, which prompted intensive care unit admission for vasopressor support and hemodialysis. She had a significant workup for the cause of her persistent fevers. CT scan of abdomen, pelvis and chest and a pelvic ultrasound were negative for any malignancy. Rheumatologic and infectious workup was also unrevealing including TB, Malaria, Hepatitis, Lyme Disease, HIV, ANA and ANCA. Further investigation revealed anemia, thrombocytopenia, markedly elevated serum ferritin and hypertriglyceridemia. As no definite source was identified, a bone marrow biopsy was collected. Given the constellation of symptoms a diagnosis of HLH was considered and the patient was transferred to a tertiary care center for further management. Upon further investigation she was found to have a significant elevated plasma Epstein Barr Virus viral load with bone marrow biopsy results showing macrophages with signs of hemophagocytosis. Patient was started on HLH treatment with IVIG and immunosuppressive therapy with etoposide, dexamethasone, and acyclovir.
Discussion: Hemophagocytic Lymphohistiocytosis (HLH) is a rare disorder with an estimated yearly incidence of 1 in 800,000 in the adult population. Impaired natural killer (NK) cells and cytotoxic T lymphocytes cause a hyperinflammatory response with activated macrophages producing cytokines. Ideally meeting 5 ofthe 8 criteria makes the diagnosis of HLH from the HLH-2004 trial. Some of the features include high-grade fever, splenomegaly, as well as biomarkers such as elevated ferritin, increased soluble interleukins, high triglycerides and cytopenias. When possible, therapy in the acquired
form is aimed at the underlying disease trigger. When the trigger is unknown, therapy is aimed at destroying immune cells. This therapy is
based on the HLH-94 protocol, which includes weekly treatments with etoposide and dexamethasone as well as cyclosporine. Often the greatest obstacle in survival of HLH patients is early diagnosis. Mortality of untreated HLH is high one retrospective study of adults with HLH
estimating 43%. Prompt recognition of the syndrome is key to survival in the affected individuals.
Conclusions: Hemophagocytic Lymphohistiocytosis (HLH) is a clinical syndrome of pathological immune activation with dysregulation which manifests as systemic inflammation, including high grade fevers, cytopenias, multi-organ failure, coagulopathy and death. The syndrome can be caused by genetic mutation of the cytotoxic function of the immune system or it can be activated by acquired conditions, including infectious, auto immune, metabolic or malignant conditions. Primarily studied in the pediatric population, HLH can occur in any age and is often fatal if there is delay in recognition and/or treatment.